First evidence of altered microbiota and intestinal damage and their link to absence epilepsy in a genetic animal model, the WAG/Rij rat.
Animals
Anti-Bacterial Agents
/ pharmacology
Anticonvulsants
/ pharmacology
Bacteroidetes
Butyrates
/ metabolism
Colon
/ pathology
DNA, Bacterial
/ analysis
DNA, Ribosomal
/ genetics
Disease Models, Animal
Electroencephalography
Epilepsy, Absence
/ genetics
Ethosuximide
/ pharmacology
Fatty Acids, Volatile
/ metabolism
Fecal Microbiota Transplantation
Firmicutes
Gastrointestinal Microbiome
/ drug effects
Gastrointestinal Motility
Haptoglobins
/ metabolism
Ileum
/ pathology
Propionates
/ metabolism
Protein Precursors
/ metabolism
Proteobacteria
Rats
Rats, Wistar
Seizures
/ genetics
fecal microbiota transplantation
gut microbiota
inflammation
microbiota-gut-brain axis
seizures
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
12
09
2020
revised:
23
12
2020
accepted:
23
12
2020
pubmed:
12
1
2021
medline:
20
4
2021
entrez:
11
1
2021
Statut:
ppublish
Résumé
A large number of studies have highlighted the important role of the gut microbiota in the pathophysiology of neurological disorders, suggesting that its manipulation might serve as a treatment strategy. We hypothesized that the gut microbiota participates in absence seizure development and maintenance in the WAG/Rij rat model and tested this hypothesis by evaluating potential gut microbiota and intestinal alterations in the model, as well as measuring the impact of microbiota manipulation using fecal microbiota transplantation (FMT). Initially, gut microbiota composition and intestinal histology of WAG/Rij rats (a well-recognized genetic model of absence epilepsy) were studied at 1, 4, and 8 months of age in comparison to nonepileptic Wistar rats. Subsequently, in a second set of experiments, at 6 months of age, untreated Wistar or WAG/Rij rats treated with ethosuximide (ETH) were used as gut microbiota donors for FMT in WAG/Rij rats, and electroencephalographic (EEG) recordings were obtained over 4 weeks. At the end of FMT, stool and gut samples were collected, absence seizures were measured on EEG recordings, and microbiota analysis and histopathological examinations were performed. Gut microbiota analysis showed differences in beta diversity and specific phylotypes at all ages considered and significant variances in the Bacteroidetes/Firmicutes ratio between Wistar and WAG/Rij rats. FMT, from both Wistar and ETH-treated WAG/Rij donors to WAG/Rij rats, significantly decreased the number and duration of seizures. Histological results indicated that WAG/Rij rats were characterized by intestinal villi disruption and inflammatory infiltrates already at 1 month of age, before seizure occurrence; FMT partially restored intestinal morphology while also significantly modifying gut microbiota and concomitantly reducing absence seizures. Our results demonstrate for the first time that the gut microbiota is modified and contributes to seizure occurrence in a genetic animal model of absence epilepsy and that its manipulation may be a suitable therapeutic target for absence seizure management.
Substances chimiques
Anti-Bacterial Agents
0
Anticonvulsants
0
Butyrates
0
DNA, Bacterial
0
DNA, Ribosomal
0
Fatty Acids, Volatile
0
Haptoglobins
0
Propionates
0
Protein Precursors
0
zonulin
0
Ethosuximide
5SEH9X1D1D
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
529-541Subventions
Organisme : Italian Ministry of University and Research (MIUR)
ID : 2015XSZ9A2
Organisme : Italian Ministry of University and Research (MIUR)
ID : 2017B9NCSX
Organisme : Italian Ministry of University and Research (MIUR)
ID : 2017YZF7MA
Organisme : Italian Ministry of Health
ID : GR-2013-02355028
Informations de copyright
© 2021 International League Against Epilepsy.
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